Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
ESMO Open. 2021 Apr;6(2):100076. doi: 10.1016/j.esmoop.2021.100076. Epub 2021 Mar 10.
Emerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate.
Material from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models.
Central Ki67 counting had excellent correlation with the results of digital image analysis (r = 0.814), but not with the diagnostic samples (r = 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HR) = 2.72, 95% confidence interval (CI) 1.19-6.21, P = 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HR = 0.50, 95% CI 0.26-0.97, P = 0.04) and OS (HR = 0.46, 95% CI 0.95, P = 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (p 0.04).
Serial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies.
越来越多的数据支持使用胸苷激酶 1（TK1）活性作为乳腺癌（BC）的预后标志物和监测反应的指标。TK1 在新辅助化疗期间的动力学对长期预后的价值尚不清楚，本研究旨在阐明这一点。
使用来自单臂前瞻性新辅助表柔比星、多西他赛和贝伐珠单抗治疗早期 BC 的 PROMIX 试验患者的材料。对基线活检进行中央和自动数字成像分析评估 Ki67。在基线和两个化疗周期后从血液样本中测量 TK1 活性。使用多变量 Cox 回归模型评估 TK1 及其动力学以及 Ki67 与无事件生存和总生存（OS）的关系。
中央 Ki67 计数与数字图像分析结果具有极好的相关性（r=0.814），但与诊断样本无关（r=0.234），而与 OS 独立相关（调整后的危险比[HR]=2.72，95%置信区间[CI]1.19-6.21，P=0.02）。化疗两个周期后 TK1 活性增加更多导致无事件生存（HR=0.50，95%CI 0.26-0.97，P=0.04）和 OS（HR=0.46，95%CI 0.95，P=0.04）改善。TK1 动力学的预后价值与 Ki67 之间存在显著的交互作用（p<0.04）。
在新辅助化疗期间连续测量血清 TK1 活性可提供 BC 患者的长期预后信息。易于获取用于 TK1 评估的连续样本，这促使在更大的研究中进一步评估。
